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    • Cell-Free DNA in the Early Course after Heart Transplantation

    J. Boehmer,C. Wasslavik,H. Wahlander,J. Sunnegardh,K. Karason,A. Ricksten,G. Dellgren

    The Journal of Heart and Lung Transplantation（2022）

    Sahlgrens Univ Hosp

    Cited 0|Views0
    Abstract
    Purpose Cell-free DNA (cfDNA) has been used as a marker of rejection after heart transplantation (HTx). The commonly reported outcome is donor fraction (DF). However, cfDNA from donor (dd-cfDNA) and recipient (rd-cfDNA) can be quantified separately. We aimed to investigate the influence of donor and recipient-derived factors as well as intraoperative measures on levels of cfDNA. Methods Blood samples were collected in parallel to the first endomyocardial biopsy in 45 patients (8 children, 37 adults) after HTx. Levels of rd- and dd-cfDNA and DF were determined using digital PCR. Regression analyses were performed with respect to the influence of donor- (age, body surface area (BSA), gender) and recipient-derived factors (age, BSA, gender, kidney function pre-HTx, ventricular assist device (VAD) pre-HTx, previous heart operation) as well as perioperative measures (operation time, ischemic graft time, early rejection, presence of acute kidney injury). Results The first biopsy was taken on a mean of 11 days after HTx (median 10, range 5-14, IQR 9-12). Mean ischemic time was 180 min (median 180, range 62-394, IQR 118-215), mean operation time was 376 min (median 333, range 174-745, IQR 239-510). Mean rd-cf-DNA levels were 190,000 copies/μl (median 140,000, range 33,000-1,400,000, IQR 83,000-200,000), mean dd-cfDNA-levels 700 copies/μl (median 400, range 150-7000, IQR 270-620). Mean DF was 0.48 (median 0.33, range 0.09-5.3, IQR 0.2-0.5). In a multiple regression model, ischemic graft time was the only factor with a statistically significant impact on levels of dd-cfDNA, but not on DF. The biggest influence on rd-cfDNA-levels was the use of a VAD pre-HTx, but this was not statistically significant. Strong correlations were seen between age and BSA of donor and recipient. Conclusion The separate quantification of both rd- and dd-cfDNA, in contrast to solely reporting DF, allows for the distinction of factors mainly influencing the recipient (such as the pre-HTx use of VAD) and the donor (such as ischemic graft time). In this proof-of-concept study, most of the investigated measures did not reach statistical significance. The correlation of ischemic graft time and dd-cfDNA (but not DF), however, shows the possibility of precisely detecting graft injury
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